Reversal of bradykinin-induced reflex tachycardia to bradycardia by captopril; evidence for prostacyclin involvement.
In conscious male New Zealand rabbits, bradykinin caused dose-dependent (0.03-1 microgram/kg i.v.) hypotension and reflex tachycardia. After inhibition of angiotensin converting enzyme (ACE, also known as kininase II) with captopril (1 mg/kg i.v.), the hypotensive effect of bradykinin was enhanced in magnitude and duration but the normally observed tachycardia was reversed to bradycardia. In rabbits treated with indomethacin to inhibit cyclooxygenase and then given captopril, the bradycardia to bradykinin reverted to tachycardia whereas the magnitude of the initial hypotensive effect was unchanged. However, inhibition of thromboxane synthetase with SQ 80,338 (1-[3-phenyl-2-propenyl]-1H-imidazole) was without effect on either bradykinin-induced hypotension or bradycardia in captopril treated rabbits. Infusion of nicotine to inhibit prostacyclin synthetase completely reversed the bradycardia induced by bradykinin in captopril-treated rabbits, an effect unrelated to ganglion blockade by nicotine since mecamylamine had no effect on the actions of bradykinin. beta-Adrenoceptor blockade with nadolol did not modify the bradycardia caused by bradykinin in captopril-treated rabbits whereas atropine methylnitrate caused a marked reduction. Captopril had no inhibitory effect on reflex tachycardia caused by nitroglycerin or acetylcholine and only reduced that caused by eledoisin. Hypotension and bradycardia resulted from giving rabbits prostacyclin (100 microgram/kg i.v.). These results suggest that the bradycardia observed in conscious rabbits to bradykinin after captopril treatment is the result of an increase in circulating bradykinin due to ACE (kininase II) inhibition leading to a vago-vagal reflex induced by the synthesis of prostaglandins, probably prostacyclin.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D002216:Captopril / Q000494:pharmacology*; D004600:Eledoisin / Q000494:pharmacology; D011464:Epoprostenol / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits
D011453:Prostaglandins; D004600:Eledoisin; D011392:Proline; D002216:Captopril; D011464:Epoprostenol; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin